Biwirubin is a yewwow compound dat occurs in de normaw catabowic padway dat breaks down heme in vertebrates. This catabowism is a necessary process in de body's cwearance of waste products dat arise from de destruction of aged red bwood cewws. First de hemogwobin gets stripped of de heme mowecuwe which dereafter passes drough various processes of porphyrin catabowism, depending on de part of de body in which de breakdown occurs. For exampwe, de mowecuwes excreted in de urine differ from dose in de faeces.[1] The production of biwiverdin from heme is de first major step in de catabowic padway, after which de enzymebiwiverdin reductase performs de second step, producing biwirubin from biwiverdin, uh-hah-hah-hah.

Biwirubin is excreted in biwe and urine, and ewevated wevews may indicate certain diseases. It is responsibwe for de yewwow cowor of bruises and de yewwow discoworation in jaundice. Its subseqwent breakdown products, such as stercobiwin, cause de brown cowor of faeces. A different breakdown product, urobiwin, is de main component of de straw-yewwow cowor in urine.

Biwirubin is very simiwar to de pigmentphycobiwin used by certain awgae to capture wight energy, and to de pigment phytochrome used by pwants to sense wight. Aww of dese contain an open chain of four pyrrowic rings.

Like dese oder pigments, some of de doubwe-bonds in biwirubin isomerize when exposed to wight. This is used in de photoderapy of jaundiced newborns: de E,Z-isomers of biwirubin formed upon wight exposure are more sowubwe dan de uniwwuminated Z,Z-isomer, as de possibiwity of intramowecuwar hydrogen bonding is removed.[3] This awwows de excretion of unconjugated biwirubin in biwe.

Some textbooks and research articwes show de incorrect geometric isomer of biwirubin, uh-hah-hah-hah.[4] The naturawwy occurring isomer is de Z,Z-isomer.

Biwirubin is created by de activity of biwiverdin reductase on biwiverdin, a green tetrapyrrowic biwe pigment dat is awso a product of heme catabowism. Biwirubin, when oxidized, reverts to become biwiverdin once again, uh-hah-hah-hah. This cycwe, in addition to de demonstration of de potent antioxidant activity of biwirubin,[5] has wed to de hypodesis dat biwirubin's main physiowogic rowe is as a cewwuwar antioxidant.[6][7][8]

In de wiver, biwirubin is conjugated wif gwucuronic acid by de enzyme gwucuronywtransferase, making it sowubwe in water: de conjugated version is de main form of biwirubin present in de "direct" biwirubin fraction, uh-hah-hah-hah. Much of it goes into de biwe and dus out into de smaww intestine. Though most biwe acid is reabsorbed in de terminaw iweum to participate in enterohepatic circuwation, conjugated biwirubin is not absorbed and instead passes into de cowon.[9]

There, cowonic bacteria deconjugate and metabowize de biwirubin into coworwess urobiwinogen, which can be oxidized to form urobiwin and stercobiwin. Urobiwin is excreted by de kidneys to give urine its yewwow cowor and stercobiwin is excreted in de faeces giving stoow its characteristic brown cowor. A trace (~1%) of de urobiwinogen is reabsorbed into de enterohepatic circuwation to be re-excreted in de biwe.[10]

Under normaw circumstances, a tiny amount of urobiwinogen, if any, is excreted in de urine. If de wiver's function is impaired or when biwiary drainage is bwocked, some of de conjugated biwirubin weaks out of de hepatocytes and appears in de urine, turning it dark amber. However, in disorders invowving hemowytic anemia, an increased number of red bwood cewws are broken down, causing an increase in de amount of unconjugated biwirubin in de bwood. Because de unconjugated biwirubin is not water-sowubwe, one wiww not see an increase in biwirubin in de urine. Because dere is no probwem wif de wiver or biwe systems, dis excess unconjugated biwirubin wiww go drough aww of de normaw processing mechanisms dat occur (e.g., conjugation, excretion in biwe, metabowism to urobiwinogen, reabsorption) and wiww show up as an increase in urine urobiwinogen, uh-hah-hah-hah. This difference between increased urine biwirubin and increased urine urobiwinogen hewps to distinguish between various disorders in dose systems.[12]

Unconjugated hyperbiwirubinaemia in a newborn can wead to accumuwation of biwirubin in certain brain regions (particuwarwy de basaw nucwei) wif conseqwent irreversibwe damage to dese areas manifesting as various neurowogicaw deficits, seizures, abnormaw refwexes and eye movements. This type of neurowogicaw injury is known as kernicterus. The spectrum of cwinicaw effect is cawwed biwirubin encephawopady. The neurotoxicity of neonataw hyperbiwirubinemia manifests because de bwood–brain barrier has yet to devewop fuwwy[dubious– discuss], and biwirubin can freewy pass into de brain interstitium, whereas more devewoped individuaws wif increased biwirubin in de bwood are protected. Aside from specific chronic medicaw conditions dat may wead to hyperbiwirubinaemia, neonates in generaw are at increased risk since dey wack de intestinaw bacteria dat faciwitate de breakdown and excretion of conjugated biwirubin in de faeces (dis is wargewy why de faeces of a neonate are pawer dan dose of an aduwt). Instead de conjugated biwirubin is converted back into de unconjugated form by de enzyme β-gwucuronidase (in de gut, dis enzyme is wocated in de brush border of de wining intestinaw cewws) and a warge proportion is reabsorbed drough de enterohepatic circuwation.

Biwirubin is degraded by wight. Bwood cowwection tubes containing bwood or (especiawwy) serum to be used in biwirubin assays shouwd be protected from iwwumination, uh-hah-hah-hah. For aduwts, bwood is typicawwy cowwected by needwe from a vein in de arm. In newborns, bwood is often cowwected from a heew stick, a techniqwe dat uses a smaww, sharp bwade to cut de skin on de infant's heew and cowwect a few drops of bwood into a smaww tube. Non-invasive technowogy is avaiwabwe in some heawf care faciwities dat wiww measure biwirubin by using an instrument pwaced on de skin (transcutaneous biwirubin meter)

Note: Conjugated biwirubin is often incorrectwy cawwed "direct biwirubin" and unconjugated biwirubin is incorrectwy cawwed "indirect biwirubin". Direct and indirect refer sowewy to how compounds are measured or detected in sowution, uh-hah-hah-hah. Direct biwirubin is any form of biwirubin which is water-sowubwe and is avaiwabwe in sowution to react wif assay reagents; direct biwirubin is often made up wargewy of conjugated biwirubin, but some unconjugated biwirubin (up to 25%) can stiww be part of de "direct" biwirubin fraction, uh-hah-hah-hah. Likewise, not aww conjugated biwirubin is readiwy avaiwabwe in sowution for reaction or detection (for exampwe, if it is hydrogen bonding wif itsewf) and derefore wouwd not be incwuded in de direct biwirubin fraction, uh-hah-hah-hah.

Totaw biwirubin (TBIL) measures bof BU and BC. Totaw biwirubin assays work by using surfactants and accewerators (wike caffeine) to bring aww of de different biwirubin forms into sowution where dey can react wif assay reagents. Totaw and direct biwirubin wevews can be measured from de bwood, but indirect biwirubin is cawcuwated from de totaw and direct biwirubin, uh-hah-hah-hah.

Indirect biwirubin is fat-sowubwe and direct biwirubin is water-sowubwe.[17]

The biwirubin wevew found in de body refwects de bawance between production and excretion, uh-hah-hah-hah. Bwood test resuwts shouwd awways be interpreted using de reference range provided by de waboratory dat performed de test. The SI units are umow/L. Typicaw ranges for aduwts are:[20]

Urine biwirubin may awso be cwinicawwy significant.[29] Biwirubin is not normawwy detectabwe in de urine of heawdy peopwe. If de bwood wevew of conjugated biwirubin becomes ewevated, e.g. due to wiver disease, excess conjugated biwirubin is excreted in de urine, indicating a padowogicaw process.[30] Unconjugated biwirubin is not water-sowubwe and so is not excreted in de urine. Testing urine for bof biwirubin and urobiwinogen can hewp differentiate obstructive wiver disease from oder causes of jaundice.[12]

Biwirubin was discovered by Rudowf Virchow in 1847.[31]) It is not awways distinguished from hematoidin, which one modern dictionary defines as synonymous wif it[32] but anoder defines as "apparentwy chemicawwy identicaw wif biwirubin but wif a different site of origin, formed wocawwy in de tissues from hemogwobin, particuwarwy under conditions of reduced oxygen tension, uh-hah-hah-hah."[33]